This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The broadly neutralizing human monoclonal antibody 2F5 targets a highly conserved region of HIV envelope (membrane proximal external region), effectively neutralizes HIV, and is of considerable interest in vaccine development. Previously we showed that 2F5 IgG was secreted in mucosal tissues following intravenous infusion, and showed that 6 hrs post infusion, substantial 2F5 IgG was detected in vaginal secretions. To cross-validate functional mucosal antibody in vitro assays with protection against vaginal challenge, we challenged rhesus macaques with SHIV-BAL following infusion with varying dilutions of 2F5 IgG, and measured mucosal and systemic levels of antibody, and plasma viremia. Macaques intravenously infused with 2F5 were protected against vaginal SHIVBAL transmission in a dose-dependent manner. Animals intravenously infused with 25-50mg/kg 2F5 were completely protected against vaginal transmission (n=5), whereas 2/5 and 0/5 macaques were protected when infused with 5mg/kg, or placebo respectively.